The regulation of the gene coding for the Met-and Leu-enkephalin precursor preproenkephalin is under investigation. Relative amounts of preproenkephalin mRNA in rat and bovine brain were determined by two methods: (1) cell-free translation of mRNA and immunoprecipitation of [35S]preproenkephalin with antibodies against either Met-enkephalin-Arg6-Phe7 or bovine proenkephalin(1-72); and (2) mRNA blot hybridization using a cloned 32p-labeled human preproenkephalin cDNA probe. Translation of rat striatum or hypothalamus mRNA resulted in the synthesis of a major preproenkephalin species of apparent Mr 30,000 and an unexpected minor putative prepro-enkephalin species of apparent Mr 31,000. The relative abundances of preproenkephalin mRNA in gross regions of the rat brain were as follows: striatum 2 greater than hypothalamus greater than cerebellum, cerebral cortex. Treatment of rats with haloperidol, a dopamine-receptor blocker with anti-schizophrenic activity resulted in an 86% increase in Met-enkephalin content and a 70-110% increase in the abundance or relative translational activity of preproenkephalin mRNA in striatum but not in hypothalamus. This result suggests that preproenkephalin gene expression in striatal neurons is under an inhibitory control by dopaminergic neurons. Treatment of rats with lithium chloride for 5 days resulted in a 66% increase in Met-enkephalin content but only a 25-29% increase in preproenkephalin mRNA activity in the striatum. In another study, the electrophysiological properties of mouse anterior pituitary AtT-20/D16 cells, which secrete the beta-endorphin/corticotropin family of peptides, were investigated. The spontaneous bursting potentials of these cells consists of fast Na+ and slow Ca++ components, as well as a Ca++ dependent K+ conductance. Addition of beta-adrenergic agonists led to increases in burst frequency, cyclic AMP levels, and beta-endorphin secretion that were blocked by beta-adrenergic antagonists.